As described in the previous annual reports, we expressed and purified two recombinant preS1 peptides (rpreS1) of hepatitis B surface antigen, i.e., a 91 amino acid (AA) wild-type peptide and a tyrosine-substituted 90 AA mutant peptide. Binding of either 125I-labeled rpreS1 peptide to a crude plasma membrane (pm) preparation from an autopsied human liver specimen was not significant. However, in the presence of anti-rpreS1 (which was produced by immunizing rabbits with the wild-type rpreS1 but recognizes both wild-type and mutant peptides), a high affinity binding was observed. The binding to pm appeared to be due to immune complexes formed between rpreS1 and anti-rpreS1. This Ag-Ab binding reached equilibrium within 20 minutes at room temperature. The binding was saturable with labeled immune complexes at 10-9 M when the pm preparation was kept constant. When the labeled rpreS1 was kept constant, increasing levels of either pm or anti- rpreS1 enhanced the binding. Neither hepG2 cells nor monocytes isolated from human blood showed any binding. The binding was blocked when pm was preincubated with unlabeled rpreS1 but not with anti-rpreS1. However, no binding was observed with (Fab')2 produced by digesting the intact IgG of anti-rpreS1 with pepsin. Thus, the binding appeared to be Fc receptor mediated. Preliminary results indicated that preincubation of pm with monoclonal antibodies to FcRI, FcRII and FcRIII had no effect on the binding of the labeled rpreS1-anti-rpreS1 complexes to pm. We have yet to determine whether such binding is specific to human hepatocytes. The significance of such binding of preS1 in the presence of its antibody remains to be investigated.